An oncolytic virus preferentially replicates in and lyses tumor cells while not exhibiting activity in non-transformed normal host cells. Several oncolytic viruses have been used in clinical trials with limited results due to limited replicative effect of oncolytic viruses and lack of an effective delivery system that specifically targets the metastatic tumor sites. Two commonly used oncolytic viruses include vesicular stomatitis virus (VSV) and adenovirus. VSV rapidly replicates and induces apoptosis in tumor cells, but not normal cells. The adenovirus, AdlTRAIL-EI, is a recombinant adenovirus with the viral replicative gene, EI, as well as the gene for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) driven by human telomerase reverse transcriptase promoter (hTERT). This virus has been shown to replicate only in cells in which telomerase is constitutively active (i.e., tumor cells) and has been shown safe and effective as an oncolytic virus in murine models.
The use of tumor targeting carriers has shown some promise in increasing tumoricidal effects of oncolytic viruses. Monocyte cell lines, T cells, and NKT cells have all been employed with limited success in attempts to find suitable tumor targeting carriers. It is possible to eliminate tumor cells from lymphoid organs when employing T cells as oncolytic carriers [see, Ilett et al. 2009 Gene Ther 16(5):689-99]. The effect obtained, however, was due to T cell tropism for lymphoid organs. This approach is therefore ineffective for targeting tumor cells in non-lymphoid organs. Creating genetically engineered T cells for tumor targeting would also be time consuming and labor intensive. Other candidate carriers for oncolytic viruses and other anti-tumor agents are therefore needed for the treatment of tumors, both in lymph nodes and in non-lymphoid organs.